Authors
Alexandra Snyder, Vladimir Makarov, Taha Merghoub, Jianda Yuan, Jesse M Zaretsky, Alexis Desrichard, Logan A Walsh, Michael A Postow, Phillip Wong, Teresa S Ho, Travis J Hollmann, Cameron Bruggeman, Kasthuri Kannan, Yanyun Li, Ceyhan Elipenahli, Cailian Liu, Christopher T Harbison, Lisu Wang, Antoni Ribas, Jedd D Wolchok, Timothy A Chan
Publication date
2014/12/4
Journal
New England Journal of Medicine
Volume
371
Issue
23
Pages
2189-2199
Publisher
Massachusetts Medical Society
Description
Background
Immune checkpoint inhibitors are effective cancer treatments, but molecular determinants of clinical benefit are unknown. Ipilimumab and tremelimumab are antibodies against cytotoxic T-lymphocyte antigen 4 (CTLA-4). Anti–CTLA-4 treatment prolongs overall survival in patients with melanoma. CTLA-4 blockade activates T cells and enables them to destroy tumor cells.
Methods
We obtained tumor tissue from patients with melanoma who were treated with ipilimumab or tremelimumab. Whole-exome sequencing was performed on tumors and matched blood samples. Somatic mutations and candidate neoantigens generated from these mutations were characterized. Neoantigen peptides were tested for the ability to activate lymphocytes from ipilimumab-treated patients.
Results
Malignant melanoma exomes from 64 patients treated with CTLA-4 blockade were characterized with the use of massively …
Scholar articles
A Snyder, V Makarov, T Merghoub, J Yuan… - New England Journal of Medicine, 2014